revised April 3, 1999
Thalassemia and Hepatitis
Blood transfusions have greatly improved the length and quality of life for patients with thalassemia major. People with the condition live far longer than the five to ten years that was common when Thomas Cooley first described the condition. The bone and facial deformities that Cooley noted fortunately are now uncommon in most countries. These benefits have come with a price, however. The haunting specters for patients with transfusion-dependent thalassemia are iron overload on the one hand, and hepatitis on the other. This document reviews some of the challenges posed by hepatitis.
What is hepatitis?
Hepatitis is inflammation of the liver. Many insults to the liver can cause inflammation, including toxins (such as aflatoxin), drugs (such as ethanol) as well as a host of viruses. The liver cells (called hepatocytes) begin to die, triggering a stereotypic response in which scar tissue forms (fibrosis). As the quantity of scar tissue increases, the number of healthy hepatocytes declines. Eventually, too few hepatocytes remain to perform the vital functions of the organ. One of the most prominent indications of problems is the development of jaundice or yellowing of the skin and whites of the eyes. Jaundice indicates that too few healthy liver cells exist to dispose of the waste pigment called bilirubin.
The liver is one of the few organs that can regenerate, or grow back if a substantial portion of it is removed. For this reason, a person who has half their liver removed after abdominal trauma in an automobile accident can recover complete function over several years. When the liver is damaged by inflammation, strands of fibrous tissue course through the organ. The liver cells try to regrow, but are confined by the bundles of fibrous tissue. Small nodules of growing, regenerating liver often develop among the bands of fibrous tissue. The development of these regenerating nodules is called cirrhosis. As the areas of cirrhosis expand, they further compromise liver function. Eventually, the combination of cirrhosis and inflammation causes liver failure and death.
Hepatitis in patients with thalassemia
Patients with thalassemia acquire hepatitis most often from viruses contracted with blood transfusions. Fortunately, advances in detection of blood-borne viruses has greatly diminished the risk of infection with blood transfusion. The number of different types of hepatitis viruses exist, of which a number have been characterized (Table 1). Over time, key problematic hepatitis virus for patients with thalassemia has changed. For many years, the hepatitis B virus was the major incubus for patients with thalassemia (or any disorder requiring chronic transfusion). The advent of new screening techniques reduced substantially the incidence of infection with this virus. The development of a new, effective vaccine has further reduced the magnitude of the problem of hepatitis B.
Table 1. Infectious Risks with Blood Transfusion
Adapted from Goodnough, et al, New England Journal of Medicine 340: 440, 1999
|Hepatitis A virus||1/1,000,000||Transient, mild hepatitis|
|Hepatitis B virus||1/30,000 to |
- acute hepatitis
- chronic hepatitis
|Hepatitis C virus||1/30,000 to |
- acute hepatitis
- chronic hepatitis
|HIV virus||1/200,000 to |
|HTLV types I and II||1/250,000 to |
As medical science overcame many of the difficulties that made hepatitis B such a challenge, another viral agent moved to the forefront. Hepatitis C was present in the blood supply all along, but we lacked a means of detecting it reliably until recently. Prior to its identification, hepatitis C was included in the group of viruses that we called "non-A, non-B". We knew that there was a group of blood borne viruses that caused hepatitis that were neither the then characterized hepatitis A or hepatitis B viruses. The key problem with the hepatitis C virus is its propensity to produce chronic, active hepatitis. The virus smolders along, slowly damaging an increasing number of hepatocytes. Over the course of many years, fibrosis and cirrhosis develops commonly. End-stage liver disease develops commonly. The slow progression does give time to intervene with antiviral agents, however. A recent report from Italy found that about 15% of patients had been exposed to hepatitis C (1). The conversion rate was about 5 per 1,000 person-years. Patients who had substantial iron overload (ferritin levels greater than 3,000) had a much greater incidence of active liver injury than those with lesser iron burdens. Current efforts to control hepatitis C infection focus on a combination of interferon-alpha and ribavirin (2,3). Initial reports are promising for combination drug therapy. Other anti-viral approaches doubtless will be developed in the future. The long duration of hepatitis C infection means that patients currently infected with the virus could receive effective therapy in the future.
Another viral agent called hepatitis virus G has recently been identified (4). Little is known about the long-term effects of this virus. However, studies to date suggest that the agent may not produce significant liver damage (5). Further work is needed to better characterize this new virus and is possible interaction with other hepatitis viruses.
- Prati D, Zanella A, Farma E, et al. 1998. A multicenter prospective study on the risk of acquiring liver disease in anti-hepatitis C virus negative patients affected from homozygous beta-thalassemia. Blood 92:3460-3464.
- Telfer PT, Garson JA, Whitby K, et al. 1997. Combination therapy with interferon alpha and ribavirin for chronic hepatitis C virus infection in thalassaemic patients. Br J Haematol 98:850-855.
- Wonke B, Hoffbrand AV, Bouloux P. 1998. New approaches to the management of hepatitis and endocrine disorders in Cooley's anemia. Ann N Y Acad Sci 850:232-241.
- Prati D, Zanella A, Bosoni P, et al. 1998. The incidence and natural course of transfusion-associated GB virus C/hepatitis G virus infection in a cohort of thalassemic patients. The Cooleycare Cooperative Group. Blood 91:774-777.
- Zemel R, Dickman R, Tamary H, et al. 1998. Viremia, genetic heterogeneity, and immunity to hepatitis G/GB-C virus in multiply transfused patients with thalassemia. Transfusion 38:301-306.